Long noncoding RNA ZFAS1 promotes gastric cancer cells proliferation by epigenetically repressing KLF2 and NKD2 expression

Abstract

Recently, long noncoding RNAs have been emerged as critical regulators of human disease and prognostic markers in several cancers, including gastric cancer. In this study, we globally assessed the transcriptomic differences of lncRNAs in gastric cancer using publicly available microarray data from Gene Expression Omnibus (GEO) and identified an oncogenetic lncRNA ZFAS1, which may promote gastric tumorigenesis. ZFAS1 has been found to be upregulated and function as oncogene in colorectal cancer and hepatocellular carcinoma, but its expression pattern, biological function and underlying mechanism in gastric cancer is still undetermined. Here, we reported that ZFAS1 expression is also overexpressed in gastric cancer, and its increased level is associated with poor prognosis and shorter survival. Knockdown of ZFAS1 impaired gastric cancer cells proliferation and induced apoptosis in vitro, and inhibited tumorigenicity of gastric cancer cells in vivo. Mechanistically, RNA immunoprecipitation and RNA pull-down experiment showed that ZFAS1 could simultaneously interact with EZH2 and LSD1/CoREST to repress underlying targets KLF2 and NKD2 transcription. In addition, rescue experiments determined that ZFAS1 oncogenic function is partly dependent on repressing KLF2 and NKD2. Taken together, our findings illuminate how ZFAS1 over-expression confers an oncogenic function in gastric cancer.

Upregulation of long noncoding RNA zinc finger antisense 1 enhances epithelial–mesenchymal transition in vitro and predicts poor prognosis in glioma

“…In this study, we investigated the function of ZFAS1 in glioma for the first time and detected that ZFAS1 was remarkably upregulated in glioma tissues compared with normal brain tissues. Importantly, this phenomenon was correlated with a shorter survival, suggesting that the expression of ZFAS1 may be used as a diagnostic and prognostic marker for glioma, which was compatible with the research results by Li et al 29 and Nie et al 30 in hepatocellular carcinoma and gastric cancer patients. Since the clinical prognostic biomarkers were required to be highly constant and reproducible, but we conducted a relative quantitative method (qRT-PCR) in our research.…”

“…28 However, recent studies have shown that ZFAS1 was amplified in hepatocellular carcinoma, colorectal and gastric cancer, and associated with their poor prognosis. 25,29,30 However, the implication of ZFAS1 in glioma progression was still unclear. In this study, we investigated the expression of lncRNA ZFAS1 in glioma tissues as well as in normal brain tissues and further explored the relationship between ZFAS1 and clinicopathological features as well as prognosis of glioma patients.…”

Prognostic and clinicopathological role of long non-coding RNA ZFAS1 in various carcinomas

“…However, there were opposite findings that elevated lncRNA ZFAS1 occurred in gastric cancer, hepatocellular carcinoma and glioma. The function of lncRNA ZFAS1 in cancer cells might be cell type-dependent [12][13][14][15][16][17][18][19][20]. Therefore, we need a systematical and comprehensive meta-analysis to explore whether overexpression of ZFAS1 in tumor are related to worse outcome.…”

“…According to the inclusion and exclusion criteria, 747 patients from 8 eligible studies were included in this meta-analysis [12][13][14][15][16][17][18][19]. The screening process was shown in Figure 1.…”

“…Moreover, emerging evidence indicated that the upregulated lncRNA ZFAS1 promoted tumor metastasis of both HCC and ovarian cancer cell through miR-150-dependent manner [14]. Nie et al also revealed that lncRNA ZFAS1 could mediate the carcinogenic effects in GC partially through silencing the KLF2 and NKD2 expression by binding with PRC2 and LSD1 [19]. Epithelial-Mesenchymal Transition (EMT) was mentioned in one study that the author suggested that lncRNA ZFAS1 induce EMT by elevating ZEB1 expression [12].…”